Laulimalide (1) and isolaulimalide (2), also known as fijianolides, were originally isolated as cytotoxic agents from the Indonesian sponge Hyatella sp. (E. Quinoa et al., xe2x80x9cFijianolides, polyketide heterocycles from a marine sponge,xe2x80x9d J. Org. Chem., 1988, 53, 3642; D. G. Corley et al., xe2x80x9cLaulimalides. New potent cytotoxic macrolides from a marine sponge and a nudibranch predator,xe2x80x9d J. Org. Chem. 1988, 53, 3644-3646), and later found along with neolaulimalide (3) in the Okinawan sponge Fasciospongia rimosa (Jefford et al., xe2x80x9cStructures and absolute configurations of the marine toxins, latrunculin A and laulimalide,xe2x80x9d 1996, Tetrahedron Letts. 37: 159-162; Higa et al., xe2x80x9cThree new cytotoxic macrolides from a marine sponge,xe2x80x9d PCT publication No. WO 97/10242). The absolute structure of natural (xe2x88x92)-laulimalide has been determined by X-ray crystallography. 
A number of total syntheses of laulimalide have been reported. See Ghosh et al., 2001, xe2x80x9cTotal synthesis of microtubule-stabilizing agent (xe2x88x92)-laulimalide,xe2x80x9d J. Org. Chem. 66: 8973-8982; Paterson et al., 2001, xe2x80x9cTotal synthesis of microtubule-stabilizing agent (xe2x88x92)-laulimalide,xe2x80x9d Org. Letts.: 3149-3152; Enev et al., 2001, xe2x80x9cMacrocyclization via allyl transfer: total synthesis of laulimalide,xe2x80x9d J. Am. Chem. Soc. 123: 10764-10765; Ghosh et al., 2000, xe2x80x9cTotal synthesis of (xe2x88x92)-laulimalide,xe2x80x9d J. Am. Chem. Soc. 122: 11027-11028.
A mechanism-based screening program aimed at isolating novel microtubule-directed anticancer agents revealed both laulimalide and isolaulimalide to be potent stabilizers of microtubules, similar to paclitaxel. See S. Mooberry et al., 1999, Cancer Res., 59, 653-660; Mooberry and Davidson, xe2x80x9cLaulimalide compounds as microtubule stabilizing agents,xe2x80x9d PCT Publication No. WO 01/54689, incorporated herein by reference.
Because of the problems associated with the use of paclitaxel such as low solubility and resistance, there is an increasing need for alternative anti-cancer compounds. The present invention provides such compounds.